Surface analysis by mass spectrometry (MS) has traditionally been performed with a sample positioned in the vacuum environment of an analysis instrument, applying desorption/ionization (DI) techniques such as secondary ion mass spectrometry (SIMS) or matrix-assisted laser desorption ionization (MALDI). Other notable techniques include fast atom bombardment (FAB) and plasma desorption (PD). In addition to MALDI performed under high vacuum conditions, an atmospheric pressure version of the MALDI method has been developed and is also commercially available. Methods for DI under vacuum are numerous and generally fall into one of two categories, employing either particle or photon bombardment. While SIMS uses energetic molecular or atomic clusters to eject and ionize analyte from a conductive surface, MALDI creates ions of the analyte in a sample under vacuum conditions using laser pulses. The high vacuum environment of these processes poses inherent limitations to the type of sample and to the physical size and shape of sample that can be analyzed. These limitations often make it necessary to perform several sample preparation steps prior to analysis, thus also limiting the throughput of the method.
Ambient DI methods were developed to overcome the limitations of the high vacuum DI methods and to permit the direct analysis of ordinary objects outside the vacuum chamber, in the open atmosphere of the laboratory or while the sample is in its native environment. The preeminent method in this new field is Desorption Electrospray Ionization (DESI). Instrumentation for performing DESI procedures has been commercialized by Prosolia, Inc. (Indianapolis, Ind. USA). These specially designed sampling/ionization sources can be applied directly to an object at hand, operating to remove molecules from the surface and carry ions in a stream of small volume that can be directed to a mass spectrometer for analysis. Thus DESI produces an analyzable sample that requires no pretreatment. DESI systems permit analyte molecules to be removed from their initial object environment with spatial resolution, and preserve critical chemical information without the dilution or physicochemical modifications or breakdown that characterize the conventional sample extraction or conditioning devices or protocols which rely upon chemically harsh or physically energetic operations. In most instances, these DESI ion sources operate in ambient atmosphere, opening the way for mass spectrometry to be used routinely within a clinical, medical, industrial or other field environment.
Numerous methods for analyte DI have been demonstrated since the first report of DESI in: Takats, Z., Wiseman, J M., Gologan, B. & Cooks, R. G., Mass spectrometry sampling under ambient conditions with desorption electrospray ionization, Science 306, 471-473 (2004); and since the first report of Direct Analysis in Real Time (DART) in: Cody, R. B., Laramee, J. A. & Durst, H. D., Versatile new ion source for the analysis of materials in open air under ambient conditions, Analytical Chemistry 77, 2297-2302 (2005). However, despite these recent advances in surface sampling mass spectrometry, significant challenges still remain with respect to desorption and ionization of analytes from surfaces since the analyte and the substrate may each present a wide range of different characteristics and chemical matrices.
Ideally, an ambient DI method would be minimally destructive to the sample and would limit fragmentation or break-down of the analytes. While the latter is advantageous, the former poses limitations since solvents or energetic processes are generally used to promote desorption. This capability is, however, important if direct analysis methods are to find success in uncontrolled environmental conditions that occur in field use, where irregular surface shapes having different physical and chemical properties are to be expected. Therefore, the development of new methods having the capacity to efficiently disrupt the interaction of analytes bound to or within a target surface, and to extract desired analytes for analysis in an instrument non-proximate to the device, is a highly desirable capability that is inadequately achieved by the current methods.
Another limitation of current methodologies is the requirement for precise alignment of the desorption/ionization source with the target object and with the sample-receiving inlet of the analysis instrument. An improvement to circumvent issues with misalignment was described in published United States Patent application 2008/0156985 of inventors Venter and Cooks. That published application describes a fixed geometry approach having a sprayer, a MS inlet and a sample surface brought together in a small pressure-tight enclosure. That configuration can extract desorbed material into a small volume of carrier gas that may be effectively input to a vacuum-type analysis instrument without degrading the instrument measurement capabilities. The enclosure also serves to protect the user from harmful aerosols that may be produced under particular experimental conditions. While that methodology constituted an advance, it remained restricted in its ability to be oriented properly to a target surface, since the spray and inlet are fixed within an enclosure.
U.S. Pat. No. 6,803,566 discloses a method for analyzing surface micro-arrays of analytes using an electro spray-based system. The method utilizes a probe for delivering an eluting solvent which is made to flow across a spot, for example of component disposed in a gel separation bed, eluting the target component. The solvent is in contact with the sample and forms a stable liquid junction. The prerequisite for forming a stable liquid junction between the solvent and the sample surface poses limitations on analysis. For example, the sample surface must be substantially flat and have appropriate physico-chemical properties to allow formation of the liquid junction.
Ultrasonic devices are those which operate in frequency ranges between approximately 20 kHz-10 MHz. Some devices, operating in the audible range from 10-20 KHz are also classified as ultrasonic devices. Devices that utilize ultrasonic energy are used frequently for a variety of applications and are readily recognized in various arts where the effects are used for purposes such as cleaning objects, breaking down material or emulsifying liquids. One common use of ultrasonic energy is in prophylactic dental equipment for professional tooth cleaning. Ultrasonics are also used ophthalmically for emulsification and removal of cataracts in the eye, and surgically for endoscopic destruction and removal of gall- or kidney stones. Additionally, ultrasonic surgical tools have seen increasing use for specialized fragmentation and removal of soft tissues, such as for tumor resection in the brain or uterus. Ultrasonic surgical devices operate by inducing cavitation in the biological fluid of a tissue, fragmenting the tissue into small components that can be removed from the body of the patient. These devices commonly incorporate a provision for irrigating the surgical site and a port for suctional removal of the fluid and tissue fragments from the treatment site. The material so removed is directed to waste or preserved for histological examination. See, for example, U.S. Pat. No. 4,827,911.